JP5898500B2 - Hard tissue regeneration promoter - Google Patents

Description

CROSS REFERENCE TO RELATED APPLICATION This application claims priority based on Japanese Patent Application No. 2006-256374 filed on Sep. 21, 2006, and this specification is incorporated herein by reference. To be included.
TECHNICAL FIELD The present invention relates to drugs, pharmaceutical compositions, food compositions, foods, animal feeds and the like useful for the regeneration of hard tissues.

In order to repair a defect or defect in a hard tissue, a conventional method of filling a defect or defect in a hard tissue with a filler containing artificial hydroxyapatite, dried beef bone powder, silicate glass powder, or Portland cement (patent) Reference 1), after melting a mixture of SiO ₂ (45 wt%), CaO (24.5 wt%), Na ₂ O (24.5 wt%), and P ₂ O ₅ (6 wt%) A method of forming a bone tissue by inserting a 300 to 360 μm granular material obtained by grinding into a defect or defect (Patent Document 2), a drug that promotes bone regeneration (Patent Document 3), and the like have been developed. ing.

US Pat. No. 5,769,638 JP-A-3-136664 JP 2003-55237 A

  The present invention relates to a hard tissue regeneration accelerator, a pharmaceutical composition, a food composition, a food, and an animal containing a substance useful for regeneration of a defective or deficient hard tissue that can be prepared at low cost both in terms of cost and labor. The purpose is to provide feed.

  As shown in the Examples, the present inventors promote the regeneration of the deficient hard tissue by administering diatomaceous earth under the periosteum near the portion where the hard tissue is deficient or orally administering the diatomaceous earth. As a result, the present invention has been completed.

  That is, the hard tissue regeneration promoter according to the present invention contains diatomaceous earth as an active ingredient. The hard tissue is, for example, a hard bone or a repaired dentin. The bone is, for example, an alveolar bone. The hard tissue regeneration-promoting agent according to the present invention may be administered (filled) under the periosteum, or administered into the bone marrow cavity that is missing due to extraction or the bone marrow cavity near the fractured site. Or may be administered orally.

  Moreover, the pharmaceutical composition which concerns on this invention contains diatomaceous earth as an active ingredient. The pharmaceutical composition according to the present invention may be a preparation administered under the periosteum, or may be a preparation administered into the bone marrow cavity deficient by tooth extraction or the bone marrow cavity near the fractured site. Alternatively, it may be a preparation for oral administration.

Furthermore, the food composition according to the present invention contains diatomaceous earth.
The food according to the present invention contains diatomaceous earth.
Moreover, the animal feed which concerns on this invention contains diatomaceous earth.

  In this specification, “diatomaceous earth” means sediments made of diatom remains, including marine diatomaceous earth (including diatom soft mud) on which marine diatoms are deposited, and freshwater on which freshwater diatoms are deposited. Including diatomaceous earth. The diatomaceous earth contained in the drug, pharmaceutical composition, food composition, food, animal feed and the like according to the present invention may be a fired product fired at a high temperature or a naturally dried product.

It is a figure which shows the structure of the tooth | gear demonstrated as one Embodiment of this invention. It is a figure which shows the structure of the bone demonstrated as one Embodiment of this invention. In one Example of this invention, it is a figure which shows the result of having observed the extracted tooth vicinity and the diatomaceous earth administration part vicinity by the micro focus X-ray enlarged observation apparatus after subperiosteal administration of diatomaceous earth. In one Example of this invention, it is a figure which shows the result of having observed the extracted part vicinity and the lower alveolar part by the microfocus X-ray enlarged observation apparatus after subperiosteal administration of diatomaceous earth. In one example of the present invention, bone regeneration and healing after tooth extraction or implant floor bone drilling is promoted by oral administration of diatomaceous earth. FIG. In one Example of this invention, it is a photograph which shows the result of having observed the bone regeneration by the oral administration of diatomaceous earth by the micro focus X-ray microscopic observation system with respect to the leg bone which was artificially perforated. In one Example of this invention, it is a photograph which shows the result of having observed the X-ray microscopic three-dimensional observation by the micro CT system that bone regeneration was accelerated | stimulated by oral administration of diatomaceous earth with respect to the leg bone which was artificially perforated. In these images, linear high-contrast shadows (indicated by white arrows) recognized in the vicinity of the bone and in the bone marrow cavity are all due to angiography and are not related to the findings of bone regeneration. It is a figure which shows the continuation of FIGS. 8 is a photograph showing the result of quantitative analysis of the amount of bone mineral from the X-ray microscopic image information shown in FIG. 7 in one example of the present invention. It is a figure which shows the continuation of FIGS.

  Hereinafter, embodiments of the present invention completed based on the above knowledge will be described in detail with reference to examples. In addition, when using a commercially available measuring apparatus, the protocol attached to the apparatus is used unless there is particular description.

  The objects, features, advantages, and ideas of the present invention will be apparent to those skilled in the art from the description of the present specification, and those skilled in the art can easily reproduce the present invention from the description of the present specification. it can. The embodiments and specific examples of the invention described below show preferred embodiments of the present invention and are shown for illustration or explanation, and the present invention is not limited to them. It is not limited. It will be apparent to those skilled in the art that various modifications and variations can be made based on the description of the present specification within the spirit and scope of the present invention disclosed herein.

== Pharmacological action of diatomaceous earth ==
As shown in FIG. 1, a tooth 100 is composed of enamel 10, dentin 20, cementum 80, pulp 30 and the like, and gum (gum) 40, periodontal ligament 60, cortical bone (compact bone) 71, sponge It is composed of bone 72 and the like, and is supported by periodontal tissue such as alveolar bone which is a hard tissue.

  As shown in Example 1, after extracting a tooth in a dog, the gingiva 40 adhering to the alveolar bone is peeled off along with the periosteum 50, and diatomaceous earth is embedded under the periosteum 50 covering the surface of the alveolar bone. It becomes clear that regeneration of new bone is promoted on the cortical bone 71 in the vicinity, on the bottom of the bone marrow cavity 73 in the vicinity of the defect part (alveolar bone) of the tooth 100 and on the cancellous bone 72 missing on the upper part of the bone marrow cavity 73. It was. In addition, as shown in Example 2, after extracting the teeth, the diatomaceous earth was orally administered to a dog whose inside of the alveolar bone was smoothly cut with a drill, so that a defect portion (alveolar sponge) on the cortical bone 71 or tooth 100 was obtained. It became clear that the regeneration of new bone was similarly promoted in the bone 72). Therefore, diatomaceous earth is removed or defective due to tooth extraction, implantation and fixation of implants, toxins of bacteria causing endodontic and periodontal diseases, infection, bone destruction due to expedient bone removal by surgery, resorption, fractures, etc. It has been found useful for promoting the regeneration of hard tissue.

  Further, the trunk of a hard bone, for example, a long bone 200 such as a humerus or a femur as shown in FIG. 2, is composed of a periosteum 110, a cortical bone 120, a bone marrow 130, and the like. The part is composed of periosteum 140, cortical bone 150, cancellous 160, bone marrow, etc., but such bones are also partially defective or missing due to fractures, implant placement, bacterial toxins, suppuration, etc. For example, diatomaceous earth can be administered under the periosteum 110, 140 in the vicinity thereof, administered into the bone marrow cavity, or orally, and thereby the hard tissue can be regenerated in a defective or defective part (implementation). Example 3 shows an example of lower limb bone regeneration by oral administration). Accordingly, diatomaceous earth is useful for promoting the regeneration of hard tissue in areas that are defective or defective due to fractures, implant placement, bacterial toxins, suppuration, and the like.

  Here, examples of hard tissues that can promote regeneration by diatomaceous earth include bones (alveolar bone, jawbone, femur, humerus, tibia, radius, ulna, vertebra, etc.), restoration dentin of tooth 100, and the like. Can be mentioned. The diatomaceous earth used is not particularly limited as long as it is a fossilized diatom such as marine diatomaceous earth or fresh water diatomaceous earth, or a fired or dried diatomaceous earth.

== About the drug, pharmaceutical composition, food composition, food, etc. according to the present invention ==
As described above, diatomaceous earth promotes regeneration of defective or deficient hard tissue, so diatomaceous earth is a pharmaceutical or food composition for patients in need of regeneration of defective or deficient hard tissue, It is useful as a feed composition for livestock that needs regeneration of deficient hard tissue, and a drug containing diatomaceous earth as an active ingredient is useful as a drug that promotes regeneration of deficient or deficient hard tissue. Is useful for patients who need to regenerate defective or deficient hard tissues, such as functional foods, foods for specified insurance, etc. Animal feed containing diatomaceous earth is useful for deficient or deficient hard tissues. Useful for livestock that needs to be regenerated. Moreover, since diatomaceous earth is a natural material and can be obtained in a large amount at a low cost, it is possible to provide a drug, a pharmaceutical composition, a food composition, a food, and the like according to the present invention at low cost and labor.

  The drug according to the present invention is not particularly limited as long as it contains diatomaceous earth as an active ingredient, and is a pharmacologically acceptable formulation additive depending on the site or purpose to be used, dosage form, etc. (For example, excipients, pH adjusters, binders, lubricants, disintegrating agents, flavoring agents, solvents, stabilizers, sugar coatings, preservatives, buffers, suspending agents, emulsifiers, fragrances, solubilizers Agents, colorants, thickeners, etc.). Also, agents for promoting periodontal tissue repair and regeneration, preventing bacterial infection, and suppressing inflammation, such as polyphosphates such as sodium polyphosphate, alginic acid as a wound dressing, etc. May further be included.

  The drug according to the present invention may be administered, for example, orally to humans or non-human vertebrates, or may be administered below the bone marrow cavity, periosteum 50, 110, 140, or the like. When orally administering the drug according to the present invention, it may be a tablet, capsule, granule, powder, syrup, pill or the like, and when administered under the periosteum 50, 110, 140, It may be a preparation such as an injection. These preparations can be produced by a conventional method using the above-mentioned preparation additives.

  The food according to the present invention may be any food containing diatomaceous earth, other antioxidants such as vitamins A, C, E, K and polyphenols, sweeteners such as aspartame and xylitol, sorbine Preservatives such as potassium acid and sodium benzoate, antioxidants such as sodium sulfite and sodium L-ascorbate, colorants such as turmeric and paprika, seasonings such as amino acids and meat extract, citric acid and malic acid It may further contain existing food additives such as acidulants.

  The food according to the present invention can be used in the form of, for example, supplements in the form of capsules, tablets, granules, etc., noodles (for example, udon), yogurt, candy (candy, drop, etc.), and sprinkles. However, it is not limited to these. Note that the food according to the present invention may finally have any shape such as a solid, powder, liquid, liquid, cream, or gel. The food according to the present invention is basically intended to be administered to a healthy person, but may be taken by a patient who needs to regenerate a defective or defective hard tissue.

  The animal feed according to the present invention may be anything as long as it contains diatomaceous earth. Besides, antioxidants, fungicides, binders, emulsifiers, regulators, amino acids, vitamins, minerals, pigments Further, it may further contain existing feed additives such as synthetic antibacterial agents, antibiotics, flavoring agents, flavoring agents, enzymes and viable bacteria agents.

== Usage Method of Drug, Pharmaceutical Composition, Food, etc. According to the Present Invention ==
The hard tissue regeneration promoter containing diatomaceous earth as an active ingredient may be administered parenterally to any patient having a defective or defective hard tissue, but may be administered directly to a defective or defective portion of the hard tissue. It is preferable to administer it in the vicinity of a portion that requires regeneration of hard tissue. For example, when administered to the periosteum 50, 110, 140 closest to the bone that needs to be regenerated or to the pulp cavity perforation AA, the apex 31, or the root canal 32 of the tooth 100, regeneration of the bone is promoted. Further, when the tooth 100 is defective or missing, the restoration of the repaired dentin is promoted by filling the dentin 20 or the like of the defective or missing tooth 100. In particular, when the tooth 100 is defective or missing until reaching the dental pulp 30, the dentin 20 or the like of the defective or missing tooth 100 may be filled so that the dental pulp 30 is not exposed. The administration method is not particularly limited, such as injection, application, and filling. Alternatively, a hard tissue regeneration accelerator may be administered orally to a patient having a defective or deficient hard tissue.

  In addition, diatomaceous earth may be ingested as a pharmaceutical composition or food containing diatomaceous earth as an active ingredient before the hard tissue is defective or deficient so that the hard tissue regeneration promoting action can be rapidly exhibited.

  Hereinafter, the present invention will be specifically described by way of examples. These examples are for explaining the present invention, and do not limit the scope of the present invention.

[Example 1]
Diatomaceous earth was administered subperiosteally to dogs lacking alveolar bone to promote the regeneration of new bone at the defect site.
At the time of extraction, diatomaceous earth (dried product; Chuo Kasei Co., Ltd., Chuo Silica Co., Ltd.) 0.2 g was peeled off by using a periosteum exfoliator, and dissolved in distilled water under the periosteum. Embedded. One month later, in the vicinity where diatomaceous earth was injected, a micro focus X-ray inspection apparatus P70-II (focal size: 10 μm × 10 μm) manufactured by Pony Industry Co., Ltd. was used, and a Kodak Phillips and Fuji Film Medical Co., Ltd. imaging plate HR The built-in cassette is arranged so that the geometric magnification is tripled, and the X-ray image is taken on the film (Fig. 3) or imaging plate (Fig. 4) under the imaging conditions (30KV 90μA film 15min, imaging plate 30sec). did. The imaging plate was read and observed using FCR 50000MA (FCR (Fuji Computed Radiography: Digital X-ray image diagnostic system); manufactured by Fuji Photo Film Co., Ltd.) (observation part: see FIG. 1). In addition, as a control, a dog not administered with diatomaceous earth was also observed with a microfocus X-ray magnifier. The results are shown in FIGS. In addition, the cocoon in FIG. 3 shows a diatomaceous earth administration part.

  In dogs to which diatomaceous earth is not administered, only a small amount of new bone is formed on the inner wall of the bone marrow cavity (Fig. 4) and the subperiosteal cortex (compact) bone in the lower part of the extraction cavity, as shown in Figs. Thus, in dogs to which diatomaceous earth was administered under the periosteum, the bottom of the bone marrow cavity of the tooth extraction socket (the square frame enclosed part in FIG. 3 and the round frame enclosed part in FIG. 4), the bone marrow cavity side wall (the round frame enclosed in FIG. 3) Part), on the subperiosteal cortical bone near the diatomaceous earth administration part (arrow in FIG. 3), and formation of young new bone on the lower alveolar part (arrow in FIG. 4), and in the bone marrow cavity of the extraction socket The formation of cancellous bone (V-shape in FIG. 3) was observed, and as a result of observing these portions over time, the new bone in the order of subperiosteal cortical bone → bottom of bone marrow cavity, side wall → cancellous bone in bone marrow cavity Formed. Thus, diatomaceous earth promotes bone formation by subperiosteal administration. In addition, it was found that, even when diatomaceous earth was administered under the periosteum, new bone was formed in the bone marrow cavity, so that bone neogenesis was promoted even when administered directly into the bone marrow cavity.

[Example 2]
Next, diatomaceous earth was orally administered to dogs lacking alveolar bone in order to promote regeneration of new bone at the defect site.
After extraction, 8-20 g of diatomaceous earth corresponding to 2-5% of the daily amount of feed was orally administered daily to a dog whose alveolar bone was smoothly cut with a drill. One month later, a section was prepared, and the osteogenic tissue in the vicinity of the missing alveolar bone was analyzed with calcium using EPMA (Electron Probe Micro Analyzer; Shimadzu EPMA8705, acceleration voltage 20 kV, sample absorption current 15 nA, MAP 512 × 512 point). Element mapping with silicon was performed (observed portion: see FIG. 1). The result is shown in FIG.

  As shown in FIG. 5, silicon derived from diatomaceous earth (white powdery signal in FIG. 5) is distributed inside the bone, and new bone ( In FIG. 5, a gray portion of the lost bone) was formed. In addition, formation of new bone was also observed on the cortical bone 71 (framed portion in FIG. 5). From this, it was clarified that even when diatomaceous earth was orally administered, silicon reached the bone defect site and new bone was formed. Therefore, it was concluded that diatomaceous earth is effective not only by subperiosteal administration and bone marrow cavity administration but also by oral administration.

[Example 3]
Furthermore, diatomaceous earth was orally administered in order to artificially perforate rat lower limb bones and promote regeneration of new bones in the pores.

<Sample processing>
As experimental rats, BrlHan: WIST @ Jcl (GALAS) (CLEA Japan, Inc .: 9-week-old mouse) was used, and after acclimatization, the rats were divided into groups from 2 days before the scheduled treatment date.
On the day of treatment, the lower limb bone (tibia) of the rat was exposed so as not to damage the periosteum as much as possible, and a dental implant drill (round bar) was used to inject about 2 mm in diameter and about 3 mm in depth under saline injection. A strong hole was drilled. Regarding the depth, it was confirmed that the head of the round bar completely perforated and transported the cortical bone to the bone marrow side. Thereafter, 2%, 5%, and 10% diatomaceous earth added to the standard sample CE-2 and sterilized by electron beam sterilization were orally administered and reared.
At 2 weeks, 4 weeks, and 5 weeks after perforation surgery, the left and right lower limbs were excised from each individual, separated into each side, fixed in formalin, and then stored cold until processed. For comparison, as a control, after a perforation operation, a feed containing only the standard feed CE-2 without diatomaceous earth sterilized with an electron beam was orally administered, and the individuals were reared, treated and observed.

<Sample preparation and observation method>
(1) X-ray microscopic observation with a microfocus X-ray microscopic observation system First, for the purpose of non-destructively observing a perforated wound, a lump without removing any soft tissue from bone, Pony Industry Co., Ltd. Using a micro focus X-ray inspection apparatus P70-II (focus size 10 μm × 10 μm), a cassette containing an imaging plate HR manufactured by Fuji Film Medical Co., Ltd. is arranged so that the geometric magnification is 3 times, and imaging conditions are set. X-ray magnified projection was performed at (30 KV 90 μA 10 seconds). Thereafter, the image information of the imaging plate was read with a digital X-ray diagnostic apparatus: FCR7000MA manufactured by Fuji Film Medical Co., Ltd., and X-ray microscopic images of each sample were obtained. The observation results will be described in detail below with reference to FIG.

(2) X-ray microscopic observation with micro CT system Three-dimensional structural examination of the perforated wound healing site at 2 and 4 weeks after perforation surgery using MCT-CB100MF manufactured by Hitachi Medical Co., Ltd. Went. The sample was fixed to a semi-cylindrical tube obtained by cleaving a polypropylene centrifugal settling tube in the major axis direction with a cellophane tape, and then fixed to an apparatus sample stage. The shooting conditions were set to (60 kV 100 μA 2 minutes). The observation results will be described in detail below with reference to FIG.

(3) Quantitative analysis of bone mineral density from X-ray microscopic image information using micro CT system. Micro CT image information of (2) is analyzed for bone mineral content using software TRI / 3D-BON-BMD manufactured by Ratoku System Engineering Co., Ltd. A relative change over time was compared. The bone mineral content was calibrated by referring to the cross section of the sample table polypropylene centrifuge tube and the cortical bone distal to the perforated wound as a substitute for the bone mineral content phantom. The analysis results are described in detail below with reference to FIG. In FIG. 8, the red equivalent part on the left side of the color bar maps the part where the bone mineral content is the highest, and the part where the bone mineral quantity is relatively low maps to the green equivalent part on the right side of the color bar. ing.

<result>
(1) X-ray microscopic observation with a microfocus X-ray microscopic observation system 2 weeks after perforation surgery (Figs. 6A to 6D): In the control individual (Fig. 6A), a semicircular depression close to the diameter of the drilled hole is clear In each of the diatomite administration groups (FIG. 6B: 2%, C: 5%, D: 10%), a callus-like impermeable portion was observed in the semicircular depression, and the area of As the concentration of diatomaceous earth increased, it increased in relation to the concentration. Furthermore, in the diatomite-administered group, a marked repairable thickening of cortical bone was observed on the bone marrow side of the lower bottom of the semicircular depression.
4 weeks after perforation surgery (FIGS. 6E-H): In the control individual (FIG. 6E), the semicircular depression became shallow and recovered to a dish-like depression. On the other hand, in the diatomite-administered group ((FIG. 6F: 2%, G: 5%, H: 10%), almost no such dish-like depression has already been observed, and the thickness of the healed cortical bone is determined by the administered diatomite. In the diatomite-treated group, the opacity due to bone regeneration that satisfies the semicircular depression equivalent site seen 2 weeks after the surgery was equivalent to that of the surroundings. Furthermore, a slight repair thickening of the cortical bone was observed on the bone marrow side in the vicinity of the site corresponding to the lower base of the depressed site.
5 weeks after perforation surgery (FIGS. 6I-L): The control (FIG. 6I) and the diatomaceous earth administration group (FIG. 6J: 2%, K: 5%, L: 10%) disappeared in all individuals. And recovered to almost normal cortical bone morphology. In the administration group, the repairable thickening on the bone marrow side of the cortical bone observed 4 weeks after the operation still remained tracely.
Thus, the promotion of bone regeneration in the perforated part was observed by orally administering diatomaceous earth to rats with perforated lower limb bones.

(2) X-ray microscopic observation with micro CT system 2 weeks after perforation surgery:
Volume rendering image (FIG. 7A): In the control individuals, hemispherical drilling close to the drilled drill diameter was still clearly visible. On the other hand, in the diatomaceous earth 10% administration group, a clear diameter reduction of the hemispherical perforated part was observed, and the closed healing of the perforated wound was progressing. On the other hand, in the diatomaceous earth 10% administration group, the X-ray permeability of the surrounding cortical bone was enhanced.
Sagittal cross-sectional image (FIG. 7B): In the control individuals, a semicircular depression close to the drilled drill diameter was clearly observed. In addition, the bottom of the depression still communicated with the bone marrow cavity, and the wound healing of the perforated wound and the regeneration of the cortical bone were hardly observed. On the other hand, in the diatomaceous earth 10% administration group, a clear reduction in the depth of the semicircular depression was observed, and at the bottom of the depression, traffic to the bone marrow cavity was narrowed, and signs of perforation wound healing and cortical bone regeneration were observed. It was done. On the other hand, a gap was found between the lamellar bones in the vicinity of the cortical bone, which was consistent with the findings of enhanced permeability observed in the rendered image. As a cause of this, in the diatomite administration group, mineralization of the wound by diatomite and subsequent calcification replacement are vigorous at this time, so the absorption and dissolution of bone lime components in the vicinity and the addition to the wound are coordinated. It is thought that it is because of being active.
4 weeks after perforation surgery:
Volume rendering image (FIG. 7C): In the control and administration groups, the hemispherical depression became shallow and recovered to a dish shape, but in the control individual, a clearly large perforated portion remained in the center. In the administration group, only a very small perforation remained in the center.
Sagittal cross-sectional image (FIG. 7D): Although the semicircular depression is shallow in the control individual, thickening of the cortical bone on the periosteum side is insufficient, and the thickness of all layers is also thin. On the other hand, in the administration group, a semicircular depression and a half-moon-shaped bone regeneration part having a single layer boundary were observed, and the thickness of the entire cortical bone layer recovered to almost the same as the surrounding area.

(3) Quantitative analysis of bone mineral content from X-ray microscopic image information by micro CT system 2 weeks after perforation surgery:
Volume rendering image (FIG. 8A): In both the control and administration groups, an embolizing substance having a much higher X-ray permeability than that of the surrounding area, ie, a considerably low density, was observed so as to block the semicircular depression.
Sagittal cross-section (FIG. 8B): In the control individuals, half of the depression is filled with low density embolic material, but the lower bottom is coarse and the perforation with the bone marrow cavity is not closed, No repair of the lower floor was observed with dense regenerated bone. On the other hand, in the diatomite-administered group, repair was confirmed with a dense and dense regenerative bone at the bottom. The volume of the embolic material in the depression was less than that of the control, which is presumably because cortical bone regeneration progressed faster than the control, and the replacement from the initial mineralization to calcification by the embolic material preceded the control. In the diatomite-administered group, there was a decrease in density between the cortical bone lamellae in the vicinity of the perforated part, and as mentioned above, this was due to the early mineralization of the wound by the administration of diatomite as described above. Since the subsequent calcification replacement is promoted, it is considered that the absorption and elution of bone lime components from the vicinity and the addition to the wound site are cooperatively active.
4 weeks after perforation surgery (FIG. 8C):
Volume rendering image: Although there was no significant difference, the diatomaceous earth group had higher bone density overall.
Sagittal cross-sectional image (FIG. 8D): Although the semicircular depression is shallow in the control individual, the thickness of the entire cortical bone is still thin. The bone density of the regenerated bone in the lower bottom was almost the same as that in the surrounding area. On the other hand, in the diatomite-administered group, a semicircular depression and a half-moon shaped bone regenerating part with a single layer boundary were observed, the cortical bone thickness recovered to almost the same as the periphery, and the bone density was also equivalent to the periphery. Therefore, it is considered that the bone healing of the diatomaceous earth administration group has recovered to the point where structural strength can withstand the load.

  According to the present invention, a hard tissue regeneration accelerator, a pharmaceutical composition, a food composition, a food containing a substance useful for regeneration of a defective or deficient hard tissue that can be prepared at low cost in terms of cost and labor, Animal feeds and the like can be provided.

Claims (5)

A bone regeneration promoter containing diatomaceous earth as an active ingredient,
A bone regeneration promoter characterized by being administered subperiosteally. A bone regeneration promoter containing diatomaceous earth as an active ingredient,
A bone regeneration promoter characterized by being administered to the bone marrow cavity. A medicament for treating a bone defect or defect containing diatomaceous earth as an active ingredient,
A medicament characterized by being a subperiosteal preparation. A medicament for treating a bone defect or defect containing diatomaceous earth as an active ingredient,
A pharmaceutical comprising a bone marrow cavity preparation. The bone defect or defects, tooth extraction, implantation of an implant with fixed, toxin causative bacteria of endodontic-periodontal disease, infection, suppuration, bone destruction, absorption, or claim 3 or 4, characterized in that by fracture The medicament according to 1.